The paper identifies major epidemiological threats associated with holding the XXI World Cup in 11 cities of the Russian Federationю Epidemiological conjuncture of enzootic natural focal infectious diseases of bacterial and viral etiology registered in FWC-2018 host-entities was analyzed from the standpoint of epidemiological risk. It is shown that hemorrhagic fever with renal syndrome was the most significant internal threat for the Republic of Tatarstan and Mordovia, Samara and Nizhny Novgorod Regions, Ixodidae tick-borne borreliosis-for Moscow, Saint Petersburg, and Sverdlovsk Region. The average risk of tick-borne viral encephalitis was determined for the Sverdlovsk Region. During the World Cup-2018, the probability of Crimean hemorrhagic fever occurrence existed in the Rostov Region (medium risk), West Nile fever-in Volgograd Region (medium risk). A clearer understanding of the epidemiological threats picture enabled us to formulate better strategies and possible to scientifically substantiate a set of preventive measures in areas of epidemiological risk.